Rhabdomyosarcoma With Epithelioid Features And NSD3::FOXO1 Fusion: Evidence For Reconsideration Of Previously Reported FOXO1::FGFR1 Fusion

• Published in: International journal of surgical pathology 2023-04, Vol.31 (2), p.213-220
• Main Authors: Rakheja, Dinesh, Park, Jason Y., Yang, Mary S., Martinez, Diana P., Koduru, Prasad, Wilson, Kathleen S., Garcia, Rolando, Uddin, Naseem
• Format: Article
• Language: English
• Subjects: Cytogenetics; Forkhead Box Protein O1 - genetics; Forkhead Transcription Factors - genetics; Humans; In Situ Hybridization, Fluorescence; Infant; Male; Paired Box Transcription Factors - genetics; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Rhabdomyosarcoma; Rhabdomyosarcoma - diagnosis; Rhabdomyosarcoma - genetics; Sarcoma
• ISSN: 1066-8969; 1940-2465
• DOI: 10.1177/10668969221098084

Epithelioid rhabdomyosarcoma is a rare rhabdomyosarcoma variant for which no diagnostic recurrent driver genetic events have been identified. Here we report a rapidly progressive and widely metastatic rhabdomyosarcoma with epithelioid features that arose in the thigh of a male infant. Conventional cytogenetics revealed a t(8;13)(p11.2;q14) translocation. Fluorescence in situ hybridization studies showed rearrangement of FOXO1 and amplification of its 3” end, and rearrangement of NSD3 and amplification of its 5` end. Next generation sequencing identified a NSD3::FOXO1 fusion, which is a previously unreported gene fusion. We also review the historic report of a FOXO1::FGFR1 fusion in a solid variant of alveolar rhabdomyosarcoma and propose that NSD3::FOXO1 fusion may have been the more appropriate interpretation of the data presented in that report.